This proposal is designed to study the role of early B cell factors (EBFs) in adipocyte biology. We have shown that EBF1 and EBF2 are required for fat cell development, and may play a significant role in governing gene expression and metabolism in fat cells. This proposal has three major Aims. First, we intend to characterize the mechanism of EBF1 action in adipogenesis, focusing on two recently discovered splice variants and on the role of EPAS1 as a mediator of the EBF1 pro-adipogenic effect. Second, we will investigate the role of EBF1 and EBF2 in metabolic physiology in vitro, using pair-wise gain-of-function and loss-of-function techniques. Specifically, we hypothesize that EBF1 and EBF2 repress lipogenesis and promote fatty acid oxidation in cultured fat cells. Finally, we will examine study the role of EBF1 and EBF2 in several in vivo models of adipocyte biology, including conditional gene ablation in adipocytes. These studies will help us to gain insight into novel transcriptional pathways in adipocyte biology, which should enable us to develop rational therapies for metabolic disease. PUBLIC HEALTH RELEVANCE: EBFs play an important role in governing transcriptional pathways in adipocytes. Understanding these pathways better will allow us to design rational strategies to combat diseases that involve adipocytes, such as obesity and lipodystrophy. [unreadable] [unreadable] [unreadable]